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Cerebrospinal fluid cell-free DNA methylomes recapture pediatric medulloblastoma tissue's tumor feature

ABSTRACT: Cerebrospinal fluid cell-free DNA methylomes recapture pediatric medulloblastoma tissue's tumor feature

PROVIDER: PRJNA739979 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14879168_1.fastq.gz	Fastqsanger.gz
	SRR14879168_2.fastq.gz	Fastqsanger.gz
	SRR14879169_1.fastq.gz	Fastqsanger.gz
	SRR14879169_2.fastq.gz	Fastqsanger.gz
	SRR14879170_1.fastq.gz	Fastqsanger.gz

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Cerebrospinal fluid cell-free DNA methylomes recapture pediatric medulloblastoma tissue's tumor feature

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Project description:Medulloblastoma (MB) is the most common malignant brain tumor in children. There remains an unmet need for diagnostics to sensitively detect the disease, particularly recurrences. Cerebrospinal fluid (CSF) provides a window into the central nervous system, and liquid biopsy of CSF could provide a relatively non-invasive means for disease diagnosis. CSF samples from patients with or without medulloblastoma (MB) were subjected to RNA-sequencing to identify differentially expressed transcripts. Although the transcriptomic signatures in CSF to differentiate MB subgroup separation was challenging, we were able to identify a group of gene signatures that could separate cancer from normal CSF. Our approach provides several candidate signatures that deserve further validation, including the novel circular RNA circ_463, and insights into the impact of MB on the CSF microenvironment.

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Project description:The main cause of death in medulloblastoma is recurrence associated with leptomeningeal dissemination. Although the molecular basis of medulloblastoma has received considerable attention over the past decade, the role of microRNAs (miRNAs) in the acquisition of metastatic phenotype remains poorly understood. This study aimed to identify miRNA involved in leptomeningeal dissemination and to elucidate its target mechanisms. We analyzed miRNA expression profiles of 29 medulloblastomas according to the presence of cerebrospinal fluid (CSF) seeding. The differential expressed miRNAs (DEmiRNAs) were validated on 29 medulloblastoma tissues and three medulloblastoma cells. The biological function of the selected miRNA was evaluated using in vitro studies. A total of 12 DEmiRNAs were identified including miRNA-192 in medulloblastoma with seeding. The reduced expression of miRNA-192 was confirmed in tumor seeding group and the medulloblastoma cells. Overexpression of miRNA-192 inhibited cellular proliferation targeting dihydrofolate reductase (DHFR). MiRNA-192 decreased cellular anchoring via repression of integrin subunits (Î±V, Î²1, and Î²3) and CD47. Medulloblastoma with seeding showed specific DEmiRNAs compared with those without seeding. MicroRNA-192 suppresses leptomeningeal dissemination of medulloblastoma through modulating cell proliferation and anchoring ability. leptomeningeal dissemination in 29 pediatric medulloblastoma patients

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